Chronic Obstructive Pulmonary Disease (COPD) is a worldwide public health problem and is the fourth leading cause of death in the United States (Heron et al., National Vital Statistics Reports 2009 57:1-134). COPD is characterized by irreversible airflow limitation due to obstruction in the small conducting airways and emphysematous destruction of the gas exchanging surface of the lung. Tobacco smoke is the major risk factor for COPD as 10-20% of smokers develop this disease (Fletcher and Peto British Medical Journal 1977 1:1645-8). Current theories concerning pathogenesis of COPD include an imbalance between protease and anti-protease activity, induced apoptosis of alveolar wall cells through deregulation of pathways involved in oxidative stress, angiogenesis, and chronic inflammation, and aberrant tissue remodeling and repair processes that lead to the destruction of the extra cellular matrix (ECM) in the lung. However, the etiology of the initiation and progression of COPD remain poorly understood.
Several groups have profiled gene expression in lung tissue from patients with and without COPD or between patients with varying levels of airflow obstruction in order to understand differences in gene expression related to COPD (Golpon et al., Am J Respir Cell Mol Biol 2004 31:595-600; Ning et al., PNAS 2004 101:14895-14900; Bhattacharya et al., Am J Respir Cell Mol Biol 2009 40:359-367; Spira et al., Am J Respir Cell Mol Biol 2004 31:601-610; Wang et al., Am J Respir Cell Mol Biol 2008 177:402-411). Although these studies have provided an initial look into the COPD transcriptome, their results have limited value in diagnosing COPD because they primarily relied on the use of lung function testing to define the presence or degree of COPD. Lung function testing cannot distinguish between obstruction in the small airways and emphysematous destruction of the lung parenchyma nor provide information about regional differences in disease severity.
Accordingly, a need exists for novel therapies for the treatment of emphysema and COPD as well as improved diagnostics for the presence and severity of emphysema in a subject.